Büchler P, Reber H A, Büchler M C, Roth M A, Büchler M W, Friess H, Isacoff W H, Hines O J
Department of Surgery, UCLA School of Medicine, Los Angeles, Calif 90095-6904, USA.
J Gastrointest Surg. 2001 Mar-Apr;5(2):139-46. doi: 10.1016/s1091-255x(01)80025-1.
The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the clinical significance of that overexpression is uncertain. In the present study we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor growth in certain patients with those diseases. We quantified HER2 expression in various human pancreatic cancer cell lines and studied the bioactivity of this antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed in vitro in cell lines with high levels of HER2/neu expression. Cell lines with low levels of this protein did not respond significantly to the antibody. In vivo we studied two different pancreatic cancer cell lines in an orthotopic mouse model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa-2 tumor cell line, which expressed high levels of HER2/neu. These data suggest that Herceptin treatment of patients with pancreatic cancer who express high levels of the HER2/neu oncogene may be reasonable.
HER2/neu癌基因在人类胰腺癌中过度表达,但其过度表达的临床意义尚不确定。在本研究中,我们研究了赫赛汀(一种新型重组人源化抗HER2/neu抗体)的抗肿瘤疗效,该抗体对过度表达HER2癌基因的乳腺癌和前列腺癌细胞具有细胞生长抑制活性。该抗体可能会延缓某些患有这些疾病患者的肿瘤生长。我们对各种人类胰腺癌细胞系中的HER2表达进行了定量,并在体外和体内研究了该抗体的生物活性。在体外,在HER2/neu表达水平高的细胞系中观察到赫赛汀对细胞生长的抑制作用。该蛋白水平低的细胞系对该抗体无明显反应。在体内,我们在该疾病的原位小鼠模型中研究了两种不同的胰腺癌细胞系。赫赛汀治疗抑制了表达高水平HER2/neu的MIA PaCa-2肿瘤细胞系中的肿瘤生长。这些数据表明,对表达高水平HER2/neu癌基因的胰腺癌患者进行赫赛汀治疗可能是合理的。